PROJECT SUMMARY/ABSTRACT Cardiovascular disease affects 80 million people in the US and is the leading cause of death. Significant limitations of current treatments necessitate the development of novel strategies. Cardiovascular tissue engineering is an emerging field focused on the development of biological substitutes to restore, maintain, or improve tissue function. Bioengineered 3-dimensional (3D) cardiac patches can be utilized clinically at the site of a myocardial infarction, promoting increased left ventricular contractile function. This study is focused on the fabrication of 3D heart muscle, using controlled stretch to support tissue development and testing the ability of cardiac patches to augment the function of infarcted myocardium. The proposed study is divided into three components. The first part of this study is focused on defining cell culture conditions to maximize the functional performance of 3D cardiac patches. The second part is focused on developing protocols to deliver controlled stretch to the 3D cardiac patches, in order to further increase the functional performance of cardiac patches. In the third part of this project, cardiac patches fabricated using optimized cell culture conditions and conditioned using stretch, will be implanted on the surface of infarcted hearts. The ability of the cardiac patches to augment the functional performance of failing myocardium will be studied, as a function of post-injury time and patch implantation time. Successful completion of this study will result in the development of 3D cardiac patches which will be functional closer to normal mammalian heart muscle and will also provide insight into the potential applicability of the cardiac patches in supporting functional recovery of failing myocardium.